Short-Chain Fatty Acids Reduce Oligodendrocyte Precursor Cells Loss by Inhibiting the Activation of Astrocytes via the SGK1/IL-6 Signalling Pathway

Short-chain fatty acids (SCFAs) are known to be actively involved in neurological diseases, but their roles in hypoxic-ischaemic brain injury (HIBI) are unclear. In this study, a rat model of HIBI was established, and this study measured the changes in IL-6 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), in addition to proliferation and apoptosis indicators of oligodendrocyte precursor cells (OPCs). The mechanism of action of SCFA on astrocytes was also investigated. Astrocytes were subjected to hypoxia in vitro, and OPCs were treated with IL-6. The results showed that SCFAs significantly alleviated HIBI-induced activation of astrocytes and loss of OPCs. SCFA pretreatment (1) downregulated the expression of NLRP3, IL-6, CCL2, and IP-10; (2) had no effect on the proliferation of OPCs; (3) ameliorated the abnormal expression of Bax and Bcl-2; and (4) regulated IL-6 expression via the SGK1-related pathway in astrocytes. Our findings revealed that SCFAs alleviated the loss of OPCs by regulating astrocyte activation through the SGK1/IL-6 signalling pathway.